Peter A. McCullough M.D.

McCullough, P. A., H. S. Mehta, D. P. Cork, C. M. Barker, C. Gunnarsson, S. Mollenkopf, J. Van Houten and P. Verta (2019). “The healthcare burden of disease progression in medicare patients with functional mitral regurgitation.” J Med Econ Jun 7. [Epub ahead of print].

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Objective: This retrospective database analysis estimated the incremental effect that disease progression from non-clinically significant functional mitral regurgitation (nsFMR) to clinically significant FMR (sFMR) has on clinical outcomes and costs. Methods: Medicare Fee for Service beneficiaries with nsFMR were examined, defined as those with a heart failure diagnosis prior to MR. Patients were classified as ischemic if there was a history of: CAD, AMI, PCI, or CABG. The primary outcome was time to sFMR, defined as pulmonary hypertension, atrial fibrillation, mitral valve surgery, serial echocardiography, or death, using a Cox hazard regression model. Annualized hospitalizations, inpatient hospital days, and healthcare expenditures were also modeled. Results: Patients with IHD had higher risk (Hazard Ratio = 1.22 [1.14-1.30]) for disease progression compared to patients without. The progression cohort had significantly more annual inpatient hospitalizations (non-IHD = 1.32; IHD = 1.40) than the non-progression cohort (non-IHD = 0.36; IHD = 0.34), and significantly more annual inpatient hospital days (non-IHD = 13.07; IHD = 13.52) than the non-progression cohort (non-IHD = 2.29; with IHD = 2.08). The progression cohort had over 3.5-times higher costs vs the non-progression cohort, independent of IHD (non-IHD = $12,798 vs $46,784; IHD = $12,582 vs $49,348). Conclusion: Treating FMR patients earlier in their clinical trajectory may prevent disease progression and reduce high rates of healthcare utilization and expenditures.

Zanoli, L., P. Lentini, M. Briet, P. Castellino, A. A. House, G. M. London, L. Malatino, P. A. McCullough, D. P. Mikhailidis and P. Boutouyrie (2019). “Arterial Stiffness in the Heart Disease of CKD.” J Am Soc Nephrol 30(6): 918-928.

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CKD frequently leads to chronic cardiac dysfunction. This complex relationship has been termed as cardiorenal syndrome type 4 or cardio-renal link. Despite numerous studies and reviews focused on the pathophysiology and therapy of this syndrome, the role of arterial stiffness has been frequently overlooked. In this regard, several pathogenic factors, including uremic toxins (i.e., uric acid, phosphates, endothelin-1, advanced glycation end-products, and asymmetric dimethylarginine), can be involved. Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. The increase in aortic stiffness results in increased cardiac workload and reduced coronary artery perfusion pressure that, in turn, may lead to microvascular cardiac ischemia. Conversely, reduced arterial stiffness has been associated with increased survival. Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. This review primarily discusses current understanding of the mechanisms concerning uremic toxins, arterial stiffening, and impaired cardiac function, and the therapeutic options to reduce arterial stiffness in patients with CKD.

Vijayaraghavan, K., P. A. McCullough, B. Singh, M. Gupta, E. Enas, V. Mohan, A. Misra, P. Deedwania and E. A. Brinton (2019). “Cardiometabolic-Renal Disease in South Asians: Consensus Recommendations from the Cardio Renal Society of America.” Cardiorenal Med May 10; 9(4): 240-251. [Epub ahead of print].

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BACKGROUND: Rates of cardiometabolic-renal disease are extremely high among South Asians (India, Pakistan, Bangladesh, Sri Lanka, Bhutan, the Maldives, and Nepal) residing in their home countries and worldwide. The Cardio Renal Society of America, National Kidney Foundation of Arizona, and Twinepidemic Inc. convened a task force to examine evidence and reach consensus regarding cardiometabolic-renal disease prevention in South Asians. The task force distilled the findings from 5 years of face-to-face and virtual meetings addressing questions derived from expert reviews of published data using the Delphi technique to create these consensus statements. SUMMARY: Several high-quality observational studies document the high and increasing incidence and prevalence of cardiometabolic-renal disease among South Asians, starting well before adulthood, owing to genetic, cultural, and environmental factors. Despite the need for additional prospective studies, especially randomized trials, of educational, screening, and other prevention efforts, sufficient information is already available to expand and intensify ongoing efforts in professional and lay education to help control this epidemic. The task force proposes to provide this expansion over the next 10 years through scientific and lay publications and other educational programs to promote more effective action among the public, health care professionals, payers, and regulators in screening for and treating cardiometabolic-renal risk factors and preventing disease in South Asians, starting at an early age. Key Messages: These consensus statements describe risk factors and prognoses characteristic of South Asians regarding cardiometabolic-renal diseases, to aid physician decision-making, health care system delivery, and research initiatives to improve the quality of care for South Asians worldwide.

Tecson, K. M., H. Hashemi, A. Afzal, T. A. Gong, P. Kale and P. A. McCullough (2019). “Community-Acquired Acute Kidney Injury as a Risk Factor of de novo Heart Failure Hospitalization.” Cardiorenal Med 9(4): 252-260.

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OBJECTIVES: Because patients with hospital-acquired acute kidney injury (AKI) are at risk for subsequent development of heart failure (HF) and little is known about the relation between community-acquired AKI (CA-AKI) and HF, we sought to determine if CA-AKI is a risk factor for incident HF hospitalization. METHODS: We utilized Baylor Scott & White Health databases at the primary care and inpatient hospitalization levels to identify adults without a prior history of HF who had 2 or more serum creatinine measurements within 13 months in the primary care setting. We defined CA-AKI as a serum creatinine increase >/=0.3 mg/dL or >/=1.5 times the baseline for consecutive values within a 13-month period. We created a flag for de novo HF hospitalization at 90, 180, and 365 days following CA-AKI evaluation. RESULTS: In the analyses, 210,895 unique adults were included, of whom 5,358 (2.5%) had CA-AKI. Those with CA-AKI had higher rates of comorbidities, higher rate of males (48 vs. 42%, p < 0.001), and were older (61.5 [50.3, 73.1] vs. 54.1 [42.8, 64.7] years, p < 0.001) than those who did not have CA-AKI. In total, 607 (0.3%), 833 (0.4%), and 1,089 (0.5%) individuals had an incident HF hospitalization in the 90, 180, and 365 days following the CA-AKI evaluation, respectively. After adjusting for demographic and clinical characteristics, patients with CA-AKI had >2 times the risk of de novo HF hospitalization compared with patients who did not have CA-AKI (90 days: 2.35 [1.83-3.02], p < 0.001; 180 days: 2.52 [2.04-3.13], p < 0.001; 365 days: 2.16 [1.77-2.64], p < 0.001). These multivariable models yielded strong predictive abilities, with the areas under the receiver-operating characteristic curve >0.90. CONCLUSION: After controlling for baseline and clinical characteristics, patients with CA-AKI were at approximately twofold the risk of de novo HF hospitalization (within 90, 180, and 365 days) compared with those who did not have CA-AKI. Hence, detecting CA-AKI may provide an opportunity for early intervention at the primary care level to possibly delay HF development.

Spinowitz, B. S., S. Fishbane, P. E. Pergola, S. D. Roger, E. V. Lerma, J. Butler, S. von Haehling, S. H. Adler, J. Zhao, B. Singh, P. T. Lavin, P. A. McCullough, M. Kosiborod and D. K. Packham (2019). “Sodium Zirconium Cyclosilicate among Individuals with Hyperkalemia: A 12-Month Phase 3 Study.” Clin J Am Soc Nephrol Jun 7; 14(6):798-809. May 20. [Epub ahead of print].

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BACKGROUND AND OBJECTIVES: Oral sodium zirconium cyclosilicate (formerly ZS-9) binds and removes potassium via the gastrointestinal tract. Sodium zirconium cyclosilicate-associated restoration and maintenance of normokalemia and adverse events were evaluated in a two-part, open label, phase 3 trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the correction phase, adult outpatients with plasma potassium >/=5.1 mmol/L (i-STAT Point-of-Care) received sodium zirconium cyclosilicate 10 g three times daily for 24-72 hours until normokalemic (potassium =3.5-5.0 mmol/L). Qualifying participants entered the /=65 years old; 74% had an eGFR<60 ml/min per 1.73 m(2), and 65% used renin-angiotensin-aldosterone system inhibitors. Mean time on sodium zirconium cyclosilicate was 286 days. Mean daily sodium zirconium cyclosilicate dose was 7.2 g (SD=2.6). Over months 3-12, mean serum potassium was 4.7 mmol/L (95% confidence interval, 4.6 to 4.7); mean serum potassium values less-than-or-equal-to 5.1 and less-than-or-equal-to 5.5 mmol/L were achieved by 88% and 99% of participants, respectively. Of 483 renin-angiotensin-aldosterone system inhibitor users at baseline, 87% continued or had their dose increased; 11% discontinued. Among 263 renin-angiotensin-aldosterone system inhibitor-naive participants, 14% initiated renin-angiotensin-aldosterone system inhibitor therapy. Overall, 489 (66%) participants experienced adverse events during the maintenance phase, and 22% experienced a serious adverse event. Of eight (1%) deaths, none were considered related to sodium zirconium cyclosilicate. Nine (1%) and 34 (5%) participants experienced serum potassium <3.0 and 3.0-3.4 mmol/L, respectively. CONCLUSIONS: After achieving normokalemia, individualized once daily sodium zirconium cyclosilicate was associated with maintenance of normokalemia without substantial renin-angiotensin-aldosterone system inhibitor changes for less-than-or-equal-to 12 months.